Fibrosis-4 score for screening of metabolic dysfunction-associated steatotic liver disease (MASLD): Data from a population-based sample in Tuscany.

BACKGROUND AND AIM: To verify the prevalence of positive Fibrosis-4 (FIB-4) score, a screening test for metabolic-associated liver disease, in a large population-based sample in the Tuscany Italian Region, and to identify sub-populations at higher risk which could be targeted by specific screening programs. METHODS AND RESULTS: Population-based survey performed in the Italian region of Tuscany, with Tuscany health informative system's administrative data. We included 594,923 subjects, of which 32% had available data for the FIB-4 calculation. The overall proportion of subjects with an FIB-4 value > 1.3, was 41.6% of those with available exams, and 12,8% of the whole population, whereas 5.4% and 1.7% had FIB-4 >2.67. In those younger than 80 years, FIB >1.3 had a 33.1% and 9.4%. People with diabetes mellitus had higher figures (52.8.% and 28.9% for FIB>1.3). Among subjects aged 70 years or over, 74.9% of those with available data and 38.4% of the general population had a FIB-4>1.3, whereas 32% and 16% had a FIB-4 > 2. CONCLUSIONS: The relevant proportion of FIB-4 positivity in the general population poses a significant burden for further screening with liver elastography. Targeting people with diabetes, excluding people older than 80 years and/or adopting a FIB-4 threshold of 2 in those aged more than 70 years could increase the cost-effectiveness of the screening procedures.

Risk of cardiovascular events after gestational diabetes: a retrospective population study.

AIMS: To investigate whether the risk for post-partum cardiovascular diseases (CVD) is driven by gestational diabetes (GDM), by GDM-related risk factors and/or by pre-gestational (Pre-GD) or post-gestational diabetes (Post-GD). METHODS: Women delivering in Tuscany, Italy in years 2010-2012 (n = 74,720), were identified from certificates of care at delivery and further identified as affected with GDM, Pre-GD or Post-GD through regional administrative databases. Women with GDM, Pre-GD or Post-GD were retrospectively evaluated for risk of post-partum hospitalizations for CVD (myocardial infarction or stroke; n = 728) across years 2013-2021, comparing women with different forms of diabetes to those without diabetes. Risk of CVD was assessed as odds ratio (OR 95% CI), after logistic multivariate models, considering all recorded pre-gestational characteristics as covariates. RESULTS: The adjusted OR (aOR) for post-partum CVD hospitalizations was not significantly related to GDM itself (aOR: 0.85; 0.64-1.12; p = ns), but increased in women with Pre-GD (aOR: 2.02; 1.09-3.71; p = 0.024) and Post-GD, associated or not to prior GDM (aOR; 4.21; 2.45-7.23 and respectively aOR: 3.80; 2.38-6.05; p < 0.0001 for both). In presence of pre-pregnancy maternal obesity (BMI ≥ 30 kg/m2) the aOR of CVD approximatively doubled (aOR: 1.90; 1.51-2.40); p < 0.0001, independently of GDM and of Post-GD. The adjusted risk of CVD was lower among employed women (aOR: 0.83; 0.70-0.99); p = 0.04 and significantly higher in presence of poorer education levels (aOR: 1.32; 1.11-1.57); p < 0.0001. CONCLUSION: In this population the risk of post-partum CVD was driven by Pre- and Post-GD, not by GDM alone. Pre-gestational obesity represented a major independent risk factor for post-partum CVD.

Perspectives on low-value care and barriers to de-implementation among primary care physicians: a multinational survey.

BACKGROUND: Healthcare costs are rising worldwide. At the same time, a considerable proportion of care does not benefit or may even be harmful to patients. We aimed to explore attitudes towards low-value care and identify the most important barriers to the de-implementation of low-value care use in primary care in high-income countries. METHODS: Between May and June 2022, we email surveyed primary care physicians in six high-income countries (Austria, Finland, Greece, Italy, Japan, and Sweden). Physician respondents were eligible if they had worked in primary care during the previous 24 months. The survey included four sections with categorized questions on (1) background information, (2) familiarity with Choosing Wisely recommendations, (3) attitudes towards overdiagnosis and overtreatment, and (4) barriers to de-implementation, as well as a section with open-ended questions on interventions and possible facilitators for de-implementation. We used descriptive statistics to present the results. RESULTS: Of the 16,935 primary care physicians, 1,731 answered (response rate 10.2%), 1,505 had worked in primary care practice in the last 24 months and were included in the analysis. Of the respondents, 53% had read Choosing Wisely recommendations. Of the respondents, 52% perceived overdiagnosis and 50% overtreatment as at least a problem to some extent in their own practice. Corresponding figures were 85% and 81% when they were asked regarding their country's healthcare. Respondents considered patient expectations (85% answered either moderate or major importance), patient's requests for treatments and tests (83%), fear of medical error (81%), workload/lack of time (81%), and fear of underdiagnosis or undertreatment (79%) as the most important barriers for de-implementation. Attitudes and perceptions of barriers differed significantly between countries. CONCLUSIONS: More than 80% of primary care physicians consider overtreatment and overdiagnosis as a problem in their country's healthcare but fewer (around 50%) in their own practice. Lack of time, fear of error, and patient pressures are common barriers to de-implementation in high-income countries and should be acknowledged when planning future healthcare. Due to the wide variety of barriers to de-implementation and differences in their importance in different contexts, understanding local barriers is crucial when planning de-implementation strategies.

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. METHODS: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. RESULTS: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. CONCLUSIONS: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection.

BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.

LDL-cholesterol target levels achievement in high-risk patients: An (un)expected gender bias.

BACKGROUND AND AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention. Collection of epidemiological data is crucial for monitoring healthcare appropriateness. This analysis aimed to evaluate the proportion of high-risk patients who achieved guidelines recommended LDL-C goal, and explore the predictors of therapeutic failure, with a focus on the role of gender. METHODS AND RESULTS: Health administrative and laboratory data from seven Local Health Districts in Tuscany were collected for residents aged ≥45 years with a history of major adverse cardiac or cerebrovascular event (MACCE) and/or type 2 diabetes mellitus (T2DM) from January 1, 2019, to January 1, 2021. The study aimed to assess the number of patients with optimal levels of LDL-C (<55 mg/dl for patients with MACCE and <70 mg/dl for patients with T2DM without MACCE). A cohort of 174 200 individuals (55% males) was analyzed and it was found that 11.6% of them achieved the target LDL-C levels. Female gender was identified as an independent predictor of LDL-C target underattainment in patients with MACCE with or without T2DM, after adjusting for age, cardiovascular risk factors, comorbidities, and district area (adjusted-IRR 0.58 ± 0.01; p < 0.001). This result was consistent in subjects without lipid-lowering therapies (adjusted-IRR 0.56 ± 0.01; p < 0.001). CONCLUSION: In an unselected cohort of high-risk individuals, females have a significantly lower probability of reaching LDL-C recommended targets. These results emphasize the need for action to implement education for clinicians and patients and to establish clinical care pathways for high-risk patients, with a special focus on women.

Pregestational exposure to hormonal combined contraceptives and risk of gestational diabetes: an observational retrospective population study.

AIMS: To investigate whether pregestational exposure to oral combined hormonal contraception (CHC) is associated with a rise in the risk of gestational diabetes (GDM). METHODS: Prevailing GDM was assessed for all pregnancies that occurred in Tuscany, Italy, from years 2010 to 2018, using administrative data coupled with information about CHC prescriptions in the year prior to pregnancy retrieved from the regional registry of drug prescription claims. The relation between exposure to CHC and risk of GDM, expressed as Odds Ratio: OR (95% Confidence Intervals, CI), was calculated separately based on citizenship of mothers using multiple logistic regression analysis models, after adjusting for confounders. RESULTS: Among 210,791 pregnancies from 170,126 mothers, GDM was present in 22,166 (10.5%) pregnancies. CHC prescription within 12 months before the index pregnancy was present in 9065 (4.3%) mothers. The risk of GDM was weakly but significantly higher in pregnancies exposed to pregestational CHC only in pregnancies of mothers of Italian citizenship: OR:1.11 (95% CI 1.02-1.21); p = 0.02, after adjusting for age, parity, calendar year and pregestational body-mass index. The CHC-mediated effect was no longer present in pregnancies of mothers at higher risk of GDM, such as pregestational obesity, migrating from countries at higher GDM risk or after adjusting for the entire panel of confounders including employment status, prior spontaneous abortions, and education degree. CONCLUSIONS: CHC had a modest effect on GDM risk, which became insignificant when added to basal prevailing risk factors for impaired glucose metabolism in pregnancy, such as pregestational obesity or originating from countries at high GDM risk.

Metrics of Gender Differences in Mortality Risk after Diabetic Foot Disease.

BACKGROUND: The aim of this study was to clarify any gender differences in the mortality risk of people with DFD since patients with diabetic foot disease (DFD) are at a high risk of mortality and, at the same time, are more likely to be men. METHODS: From regional administrative sources, the survival probability was retrospectively evaluated by the Kaplan-Meier method and using the Cox proportional-hazards model comparing people with DFD to those without DFD across the years 2011-2018 in Tuscany, Italy. Gender difference in mortality was evaluated by the ratio of hazard ratios (RHR) of men to women after initial DFD hospitalizations (n = 11,529) or in a cohort with prior history of DFD hospitalizations (n = 11,246). RESULTS: In both cohorts, the survival probability after DFD was lower among women. Compared to those without DFD, after initial DFD hospitalizations, the mortality risk was significantly (18%) higher for men compared to women. This excess risk was particularly high after major amputations but also after ulcers, infections, gangrene, or Charcot, with a lower reduction after revascularization procedures among men. In the cohort that included people with a history of prior DFD hospitalizations, except for the risk of minor amputations being higher for men, there was no gender difference in mortality risk. CONCLUSIONS: In people with DFD, the overall survival probability was lower among women. Compared to those without DFD after a first DFD hospitalization, men were at higher risk of mortality. This excess risk disappeared in groups with a history of previous DFD hospitalizations containing a greater percentage of women who were older and probably had a longer duration of diabetes and thus becoming, over time, progressively frailer than men.

Identification of dementia and MCI cases in health information systems: An Italian validation study.

Introduction: The identification of dementia cases through routinely collected health data represents an easily accessible and inexpensive method to estimate the prevalence of dementia. In Italy, a project aimed at the validation of an algorithm was conducted. Methods: The project included cases (patients with dementia or mild cognitive impairment [MCI]) recruited in centers for cognitive disorders and dementias and controls recruited in outpatient units of geriatrics and neurology. The algorithm based on pharmaceutical prescriptions, hospital discharge records, residential long-term care records, and information on exemption from health-care co-payment, was applied to the validation population. Results: The main analysis was conducted on 1110 cases and 1114 controls. The sensitivity, specificity, and positive and negative predictive values in discerning cases of dementia were 74.5%, 96.0%, 94.9%, and 79.1%, respectively, whereas in detecting cases of MCI these values were 29.7%, 97.5%, 92.2%, and 58.1%, respectively. The variables associated with misclassification of cases were also identified. Discussion: This study provided a validated algorithm, based on administrative data, which can be used to identify cases with dementia and, with lower sensitivity, also early onset dementia but not cases with MCI.

Covid-19 pandemic, diabetes and glycemic control: Results of a retrospective cohort study of 230.000 persons with diabetes in tuscany.

BACKGROUND AND AIMS: The COVID-19 pandemic affected the processes of routine care for chronic patients due to disrupted delivery care. The aim of the present study is to verify the COVID-19 pandemic effects on diabetes control and management. METHODS AND RESULTS: The study was designed as a retrospective observational study, performed on two cohorts of patients with diabetes in 2019 and 2020. Data used for the analyses were gathered from administrative and laboratory databases, which do not include any sensible information on COVID-19. The Tuscany Regional Health Agency is data controller for current administrative databases and has been working to produce available information for policy decision-making. In 2020, in comparison with 2019, a relevant reduction of the number of patients measuring HbA1c was observed during the March-April lockdown, and again during the second pandemic wave in Autumn. A similar pattern was observed for specialist visits for diabetes, for which the introduction of televisits only partly compensated for the reduction of traditional office visits. The number of patients receiving drugs for diabetes each week in 2020 was very similar to 2019. The mean HbA1c values and the proportion of HbA1c values > 8% for each week, were higher during the 2020 Spring and Autumn lockdown. CONCLUSION: COVID-19 pandemic negatively impacts diabetes management, reducing specialist visits and HbA1c determinations during the first and second pandemic wave. Despite a satisfactory continuity in pharmacological treatment, short-term impairment of average glycemic control was detected, particularly in Autumn.

Prevalence of chronic comorbidities in people with multiple sclerosis: descriptive study based on administrative data in Tuscany (Central Italy).

OBJECTIVE: Chronic comorbidities are common in people with multiple sclerosis (PwMS), thus worsening their prognosis and quality of life, and increasing disease burden. The aim of the present study was to evaluate the prevalence of common comorbidities in PwMS in Tuscany (Central Italy) and to compare it with the general population. METHODS: The prevalence of comorbidities, including diabetes, chronic obstructive pulmonary disease (COPD), hypertension, stroke, heart failure (HF), cardiac infarction and ischemic heart disease (IHD), was assessed in PwMS and in general population resident in Tuscany, aged > 20 years, using administrative data. RESULTS: In total, we identified 8,274 PwMS. Among them, 34% had at least one comorbidity, with hypertension being the most common (28.5%). Comparing PwMS with the general population, PwMS had a higher frequency of hypertension and stroke when considering the whole group, and of diabetes, COPD, and IHD when considering sex and age subgroups. This increased risk was especially evident in the young and intermediate age groups, where multiple sclerosis may play an important role as risk factor for some comorbidities. In PwMS, as well as in the general population, prevalence of chronic diseases was higher in males and increased with age. CONCLUSIONS: Comorbidities frequently coexist with multiple sclerosis and they may have an impact on this complex disease, from the health, clinical, and socioeconomic points of view. Therefore, a routine screening of chronic comorbidities should be a crucial step in clinical practice, as well as the promotion of healthy lifestyles to prevent the onset and to reduce their burden.

Time to Treatment Intensification in Patients Receiving DPP4 Inhibitors Versus Sulfonylureas as the First Add-On to Metformin Monotherapy: A Retrospective Cohort Study.

Background: To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a dipeptidyl peptidase inhibitor (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI). Methods: Population-based administrative data banks from four Italian geographic areas were used. Patients aged ≥18 years on MET monotherapy receiving first DPP4i or SU dispensing between 2008 and 2015 (cohort entry) were followed up to the occurrence of TI (insulin dispensing or add-on of a third non-insulin hypoglicemic >180 days after cohort entry), treatment discontinuation, switch, cancer, death, TI occurrence within, end of data availability, end of study period (31 December 2016), whichever came first. Patients on MET + DPP4i were matched 1:1 with those on MET + SU by sex, age, year of cohort entry, and data bank. Hazard Ratio (HR) and 95% confidence intervals (95%CI) were estimated using multivariable Cox regression model including matching variables and potential confounders measured at baseline. Different sensitivity analyses were performed: i) matching at 180 days after cohort entry, ii) intent to treat (ITT) analysis, iii) matching by duration of MET monotherapy, iv) matching by propensity score. Results: The matched study cohort included 10,600 patients. Overall, 763 TI were observed (4.5/100 person-years; mean follow-up = 1.6 years). The primary analysis showed no difference in time to TI between the two groups (HR = 1.02; 95% CI = 0.88-1.19). Sensitivity analyses confirmed this result, except from the ITT analysis (HR = 1.27; 1.13-1.43). Conclusion: The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification.

Mortality Risk Associated with Diabetic Foot Complications in People with or without History of Diabetic Foot Hospitalizations.

The aim of this study was to evaluate the risk of death after hospitalizations for diabetic foot (DF) complications, comparing two different cohorts of people with or without a prior history of DF hospitalizations across the years 2011 to 2018 in Tuscany, Italy. The DF complications were categorized by administrative source datasets such as: amputations (both major and minor), gangrene, ulcers, infections, Charcot and revascularizations. A further aim was to present the trend over time of the first ever incidents of diabetic foot hospitalizations in Tuscany. The eight-year-mortality rate was higher in the cohort with prior hospitalizations (n = 6633; 59%) compared with the cohort with first incident DF hospitalizations (n = 5028; 44%). Amputations (especially major ones) and ulcers had the worst effect on survival in people without basal history of DF hospitalizations and respectively in those with a history of prior DF hospitalizations. In both cohorts, revascularization procedures, when compared to ulcers, were associated with a significantly reduced risk of mortality. The prevalence rate of minor amputations showed a slightly rising trend over time. This result agrees with the national trend. Conversely, the progressive increase over time of revascularizations, associated with the fractional decrease in the rate of gangrene, suggests a trend for more proactive behavior by DF care teams in Tuscany.

Frailties and critical issues in neuromuscular diseases highlighted by SARS-CoV-2 pandemic: how many patients are still "invisible"?

Almost 90% of neuromuscular diseases (NMDs) are classified as rare diseases, defined as conditions affecting less than 5 individuals in 10.000 (0.05%). Their rarity and diversity pose specific challenges for healthcare and research. Epidemiological data on NMDs are often lacking and incomplete. The COVID-19 pandemic has further highlighted the management difficulties of NMDs patients and the necessity to continue the program of implementation of standard of care. This article summarizes the Italian experience during pandemic.

Effect of diabetes on short-term mortality and incidence of first hospitalizations for cardiovascular events after recovery from SARS-CoV-2 infection.

AIM: To evaluate the impact of diabetes and COVID-19 on all-cause-mortality and first hospitalizations for cardiovascular events (CVE): myocardial infarction or stroke, within six months after being tested positive and having recovered from SARS-CoV-2 infection. METHODS: Resident population in Tuscany, Italy of age 45-94 yr without prior hospitalization for CVE, tested positive for SARS-CoV-2 by March 1st, 2020 and afterwards recovering from COVID-19 was compared with age, gender and diabetes matched controls without infection, for incidence rate ratio (IRR) of all-cause-deaths or first CVE at six months follow up. RESULTS: 46,152 subjects of whom 4,597 with diabetes, tested positive and recovered from SARS-CoV-2 were compared with 1:1 age, gender and diabetes matched controls without infection. COVID-19 was associated with higher all-cause-mortality: IRR:1.92(95 %CI:1.63-2.25) while diabetes with increased risk of first CVE hospitalizations: IRR:2.24(2.18-4.25). Co-presence of COVID-19 and diabetes didn't add any additional excess risk. Being women and statins' use significantly reduced death risk. CONCLUSIONS: After recovery from COVID-19, independently of diabetes, all-cause-mortality risk at six months was twofold increased, while risk of first CVE hospitalization remained unmodified. Diabetes, independently of prior COVID-19, resulted in higher six-months risk of first CVE not of death. Female gender and statins' use reduced both excess risks.

Incidence of malignant neoplasms and mortality in people affected by multiple sclerosis in the epoch of disease-modifying treatments: A population-based study on Tuscan residents.

BACKGROUND: Conflicting data are currently available on the risk of malignancies in people affected by multiple sclerosis (pwMS), and the potential relative contribution to this risk of disease-modifying therapies (DMTs) is still debated. Moreover, data on the long-term prognosis of pwMS mostly derive from natural history studies and updated observations during the treatment era are lacking. METHODS: Incidence of cancer and mortality were analysed in a pwMS cohort of residents of Tuscany over a 17-year period of observation during the treatment era and compared with the rates observed in a 1:10 sex- and age-matched control population resident in the same geographical area. RESULTS: Six-hundred and sixty-one pwMS were included; median age 43 years (range 19-80); 87% affected by relapsing-remitting MS. Sixty-eight percent of the cases were exposed to DMTs over the study period. Age and sex standardized incidence of malignancy did not differ between the groups: 3.9 × 1000 (95% confidence interval, CI, 3.75-4.15) person-years and 4.1 × 1000 (95% CI 3.76-4.42) person-years in the MS and control cohorts, respectively. The most frequent cancers reported in pwMS were breast, gastrointestinal and gynaecological cancers. Standardized mortality rates were 2.0 × 1000 person-years (95% CI 1.58-2.37) and 2.4 × 1000 (95% CI 2.03-2.78) person-years in the MS and control cohorts, respectively, and did not differ between groups, also after excluding traumatic cause-of-death (1.6 vs 1.7). CONCLUSIONS: The incidence of cancer and mortality did not differ between pwMS and the general population residing in the same geographical area, suggesting that life expectancy of pwMS has improved over the treatment era.

The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes.

AIMS: To investigate whether fetal sex affects the impact of classical GDM risk factors on the diagnosis of gestational diabetes (GDM) as well as on related adverse pregnancy outcomes. METHODS: This retrospective observational study concerned 206,917 singleton live births born to 170,126 women aged 15-45 over the years 2010-2018 in Tuscany, Italy. GDM was identified by administrative data-sources in 21,613 pregnancies (10.5%) by assessing, through multiple logistic models, whether fetal sex modified the risk of GDM driven by maternal risk factors, and whether it modified the risk of adverse outcomes such as prematurity (birth ≤ 37th gestational week), large for gestational age (LGA), unplanned caesarean sections, or 5-min-Apgar-index ≤ 7 in pregnancies with GDM. RESULTS: GDM was diagnosed in 21,613 pregnancies (10.5%). Male fetal sex predicted a higher adjusted risk of GDM: OR = 1.05(95% CI: 1.01-1.07); p < 0.0009. In pregnancies with female sex, pre-pregnancy obesity amplified the risk of GDM: OR = 1.09(95% CI: 1.01-1.19); p = 0.04. In pregnancies with GDM, carrying a female fetus increased the risk of LGA associated with pregestational obesity OR = 1.45(95% CI: 1.15-1.81); p = 0.001, and in primiparous pregnancies, it protected mothers from the risk of unplanned caesarean sections OR = 0.80(95%CI: 0.67-0.92); p = 0.001. CONCLUSIONS: While male fetal sex is associated with rise in the risk of GDM, giving birth to a girl amplifies the excess GDM risk driven by pregestational obesity, thus increasing the risk of LGA in pregnancies with GDM. Additionally, female fetal sex in pregnancies with GDM seems to protect from the risk of unplanned caesarean sections in primiparous pregnancies.

SIRT1 rs7896005 polymorphism affects major vascular outcomes, not all-cause mortality, in Caucasians with type 2 diabetes: A 13-year observational study.

AIMS: SIRT1 exerts effects on ageing and lifespan, as well cardiovascular (CV) disease risk. SIRT1 gene is very polymorph with a few tagging single nucleotide polymorphisms (SNPs) so far identified. Some SNPs, including rs7896005, were associated with type 2 diabetes (T2DM). We aimed to ascertain whether this SNP may be associated with CV disease at baseline as well with these same outcomes and all-cause mortality over a 13-year follow-up. MATERIALS AND METHODS: Genotypes of SIRT1 gene were determined using TaqMan SNP assay. RESULTS: Out of 905 T2DM, 9.1% had the AA genotype, 43.2% the AG, and 47.7% the GG. Hardy-Weinberg Equilibrium was met (minor allele frequency 0.306; p = 0.8899). At baseline, there was no difference across genotypes for sex, age, diabetes duration, CV risk factors, treatments, and microangiopathy. Major CV outcomes, myocardial infarction (MI), any coronary heart disease (CHD), and peripheral artery disease (PAD) were more frequent in GG than in AA/AG (p from 0.013 to 0.027), with no association with cerebrovascular events. By fully adjusted regression, GG remained independently related to major CV outcomes, MI, CHD, and PAD. Over follow-up, we recorded 258 major CV events (28.5%; AA/AG 25.2%, GG 32.2%; p = 0.014) with an adjusted hazard ratio (HR) of GG versus AA/AG of 1.296 (95% CI 1.007-1.668, p = 0.044); 169 coronary events (18.7%; AA/AG 15.4%, GG 22.2%; p = 0.006) with HR 1.522 (1.113-2.080, p = 0.008); 79 (8.7%) hospitalisation for heart failure (AA/AG 7.0%, GG 10.6%; p = 0.045) and HR 1.457 (0.919-2.309, p = 0.109); 36 PAD (4.0%; AA/AG 2.3%, GG 5.8%; p = 0.007) with HR 2.225 (1.057-4.684, p = 0.035). No association was found with cerebrovascular events, end stage renal disease, and all-cause mortality. CONCLUSIONS: The rs7896005 SNP of SIRT1 might play a role in cardiovascular disease, mainly CHD risk in T2DM. Results call for larger association studies as well as studies to ascertain mechanisms by which this variant confers increased risk.

Gender Differences in the Risk of Adverse Outcomes After Incident Diabetic Foot Hospitalization: A Population Cohort Study.

BACKGROUND: Diabetic Foot Disease (DFD) is more prevalent among males and is associated with an excess risk of cardiovascular events or mortality. AIMS: This study aimed at exploring the risk of cardiovascular events, renal failure, and all-cause mortality after incident DFD hospitalizations, separately in males and females, to detect any gender difference in a cohort of 322,140 people with diabetes retrospectively followed up through administrative data sources in Tuscany, Italy, over the years 2011-2018. METHODS: The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations for DFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs' revascularizations (LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background of DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). RESULTS: DFD incidence rate was higher among males compared to females (1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary artery disease was significantly associated with the male gender and of stroke with the female gender. LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they were found to be associated with the risk of coronary artery disease among females to a significantly greater extent compared to males. The incident of renal failure was not associated with any DFD category. Amputations and LEAD-no proc significantly predicted high mortality risk only in females, while LLR showed reduced risk in both genders. Moreover, females had a greater risk of composite outcomes (death or cardiovascular events). Compared to the background of DFD, the risk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher after LEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascular pathogenesis, females are at an increased risk of adverse events. CONCLUSION: After incident DFD hospitalizations, females with DFD associated with amputations or arterial disease are at a greater risk of subsequent adverse cardiovascular events than those with a DFD background.

[Audit & Feedback: an example of use to improve adherence to therapies.] / Audit & Feedback: un esempio di utilizzo per migliorare l'aderenza alle terapie.

Although the Audit & Feedback (A&F) strategy is widely used in the healthcare context, a margin of uncertainty remains regarding the actual effectiveness in actually improving healthcare quality. Effectiveness research on A&F should be improved, without replicating studies and results already consolidated over the years. Comparative efficacy studies are needed in order to evaluate A&F strategies in poorly explored research areas, such as community care or home care. In these areas, a translational research framework has been developed by the Tuscan Regional Health Agency: its aim is to make the results available to the professionals involved in the territorial management of chronic patients. Doctors coordinating the territorial functional aggregations and referring community physicians are the main targets. A&F can also be a tool to improve the performance of general practitioners in their actions aimed at maintaining patients' adherence to clinical prescriptions, highlighting any significant difference between the monitored performances.